Objectives: The aim of this study was to evaluate the efficacy and safety of rituximab and tocilizumab compared with adalimumab, etanercept, and infliximab, in patients with rheumatoid arthritis not responding to first-line treatment, and to compare the efficacy and safety of rituximab versus tocilizumab in patients not responding to anti-tumor necrosis factor α (anti-TNF) therapy.

Methods: A literature search of randomized controlled trials, controlled clinical trials, and systematic reviews was performed to evaluate efficacy and safety of rituximab and tocilizumab.

Results: Twenty-four RCTs were included in this systematic review with 6,357 participants; 3,450 treated with biological DMARD and 2,907 with standard care. In patients not responding to first-line treatment, rituximab shows lower response rate in at least 50 percent improvement in the American College of Rheumatology criteria (ACR50) and ACR70 compared with etanercept, at 6 months of follow-up. Tocilizumab shows higher ACR70 response rate compared with infliximab, at the same follow-up time. Other results showed no significant differences. Indirect comparisons between rituximab and tocilizumab in patients not responding for at least one anti-TNF, shows higher ACR20 response rate for tocilizumab at 6 months of follow-up. Regarding safety, adalimumab and etanercept were associated with significant fewer withdrawals due to adverse events compared with infliximab.

Conclusions: Considering efficacy, safety, and the availability of 3 anti-TNFs in the National Medicines Formulary (adalimumab, etanercept, and infliximab), it seems appropriate to remove infliximab from the coverage, and introduce tocilizumab for patients not responding for at least one anti-TNF.